Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors examined the activity of the cyclic Somatostatin on Ethanol hypoglycemia. While the peptide is capable of increasing the plasma glucose levels of hypoglicemia starved rats, it does not increase the levels of plasma glucose in normal rats under the action of ethanol perfusion.
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PMID:[Effect of cyclic somatostatin on ethanol-induced hypoglycemia]. 4

Ethanol administration decreases GH secretion in humans and experimental animals. The mechanism of these inhibitory effects was investigated by evaluating the spontaneous secretory pattern of GH in chronically cannulated unanesthetized rats, plasma insulin-like growth factor-I (IGF-I) concentrations, and hypothalamic GH-releasing hormone (GHRH) and somatostatin, and pituitary GH mRNA levels. Body weight gain was reduced in ethanol (5%)-liquid diet-fed rats (n = 6) for 6 days compared to that in both isocalorically pair-fed controls (n = 6) and ad libitum-fed animals (n = 6). Spontaneous GH secretion was markedly decreased (by 75-90%) in ethanol-fed rats compared to that in pair-fed and ad libitum-fed groups, while pulsatile pattern of GH release was preserved, with secretory bursts occurring every 180-220 min in all groups. Mean 6-h plasma GH levels in ethanol-, pair-, and ad libitum-fed animals were: 18.8 +/- 4.5, 113.3 +/- 14.9, and 179.6 +/- 30.1 ng/ml, respectively (P < 0.01, ethanol vs. each control). Plasma IGF-I concentrations were decreased in the ethanol-fed rats (338 +/- 16 ng/ml) compared to those in pair-fed (427 +/- 39 ng/ml; P < 0.05) and ad libitum-fed (769 +/- 25 ng/ml; P < 0.01) rats. Ethanol treatment decreased GHRH mRNA levels to 9% of those in ad libitum-fed (P < 0.01) and 20% of those in pair-fed (P < 0.05) animals, whereas it did not significantly alter somatostatin or GH mRNA levels. The results indicate that the effects of ethanol inhibit GH secretion primarily at the hypothalamic level, resulting in impaired GHRH gene expression. Since the GHRH-GH-IGF-I axis has an important role in growth regulation, the growth retardation seen in experimental models of alcohol abuse may be a consequence at least in part of the suppressive effects of ethanol on this axis.
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PMID:Inhibitory effects of ethanol on the growth hormone (GH)-releasing hormone-GH-insulin-like growth factor-I axis in the rat. 135 62

Ethanol exerts profound effects both in ovo and in culture on neuronal phenotypic expression. In order to define more directly the neuronal growth parameters sensitive to the neurotoxic effects of ethanol, embryos were exposed to ethanol (10 mg/50 microliters/day) or saline (control) at embryonic days 1 and 2; neuron-enriched cultures prepared from these treated embryos at 3 days of embryonic age. Cultures from both groups were labeled with [3H]thymidine and assessed for effects on neuronal survival and proliferation in culture. Treatment of embryos with ethanol in ovo resulted in a marked enhancement in normal neuronal death in culture with no significant effect on proliferation. Whereas somatostatin (SRIF) had no effect on normally occurring neuronal death in control cultures, addition of SRIF (100 nM) to the culture medium attenuated the ethanol-induced neuronal cell death. Videometric analysis revealed that pretreatment of embryos with ethanol resulted in formation of more and larger aggregates as compared with controls, an effect that was augmented by addition of SRIF to the medium. The most profound effect of ethanol on growth patterns was observed in neurite outgrowth showing a marked reduction in both neurite number and length in embryos pretreated with ethanol. SRIF enhanced neurite outgrowth (neurite number and length) in cultures derived from ethanol-treated embryos. These results suggest that the ethanol-induced deficits in neuronal survival and morphology are reversible. We conclude that SRIF may enhance neuronal survival by promoting neuritic outgrowth, thus establishing the essential target cell contacts necessary for cell survival.
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PMID:Survival and proliferation in developing neuroblasts in cultures derived from embryos treated with ethanol during early neuroembryogenesis: effects attenuated by somatostatin. 168 83

Previous in vivo studies showed that systemic ethanol enhanced hippocampal neuronal responses to iontophoretically applied acetylcholine and somatostatin while having little or no effect on responses to other transmitters. We previously reported that these two agonists reciprocally regulate the non-inactivating, voltage-dependent K+ current called the M-current. Therefore, we tested ethanol superfusion on this current in rat hippocampal pyramidal neurons in vitro, using intracellular recording and single electrode voltage-clamp methods. Tetrodotoxin (TTX) was used to block Na+ spikes and synaptic transmitter release. Ethanol in low concentrations (22-44 mM), like muscarinic agonists, greatly reduced the M-current amplitude at depolarized membrane potentials and at 44 mM antagonized its augmentation by somatostatin. These changes were often accompanied by an inward baseline current with a conductance decrease. Other than a small inward current in some cells there was little or no consistent ethanol effect at resting membrane potentials. Atropine 1 microM (and TTX) did not alter the ethanol effect on the M-current. Therefore, the site of ethanol action is most likely distal to the muscarinic receptor. Ethanol reduction of the M-current, by summation of like effects, may account for the potentiation of acetylcholine responses seen in vivo and in vitro, and provides a mechanism for the excitatory effects of ethanol on some central neurons.
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PMID:Ethanol diminishes a voltage-dependent K+ current, the M-current, in CA1 hippocampal pyramidal neurons in vitro. 197 65

The effects of ethanol and related short-chain alcohols on histamine release from purified rat mast cells were compared to the effects of the alcohols on mast cell membrane properties. Concanavalin A (Con A) (9.3-2790 nM) and somatostatin (0.61-61 microM) stimulated histamine release in a concentration-dependent manner. Ethanol (10-500 mM) had little effect on histamine release itself. However, it inhibited Con A- and somatostatin-stimulated release. Con A was more sensitive to the inhibitory effects of ethanol. For example, 100 mM ethanol inhibited Con A-stimulated release by 56%, whereas somatostatin-stimulated release was reduced only 28%. Mast cell membranes were prepared and the membrane order estimated by determining the fluorescence polarization of diphenylhexatriene. Ethanol (10-500 mM) decreased the fluorescence polarization of mast cell membranes, suggesting a decrease in membrane order. The changes in membrane order by ethanol correlated (r2 = 0.99) with both the inhibition of Con A- and somatostatin-stimulated release. Changes in membrane polarization due to a temperature change from 35 degrees C to 40 degrees C also correlated with changes in receptor-stimulated histamine release. The effects of a series of alcohols related to ethanol on stimulated histamine release and mast cell membrane organization were similar to ethanol and dependent on the lipophilicity of the alcohol. These findings suggest that alcohol effects on membranes can alter receptor function and that certain receptors, e.g., Con A, are more sensitive to the membrane actions of ethanol or related alcohols than are other receptors, e.g., somatostatin.
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PMID:Correlation of ethanol's membrane actions and inhibition of receptor-stimulated histamine release from rat mast cells. 242 70

Male rats were given 10% (w/v) ethanol in drinking fluid during the first week, 15% (w/v) during the second week, 20% (w/v) during the third, and 25% (w/v) during the fourth week, at the end of which they were kept on 25% (w/v) ethanol drinking water for 3 weeks. Some animals were then allowed the withdrawal of ethanol for a period of 2 weeks or 7 weeks. No significant differences were seen for the basal and forskolin (FK)-stimulated adenylate cyclase (AC) enzyme activities in the pancreatic acinar membranes of ethanol-treated and ethanol withdrawal rats as compared to the control group. Chronic ethanol ingestion resulted in an attenuation of somatostatin(SS)-inhibited FK-stimulated AC in rat pancreatic acinar membranes. The ability of the stable GTP analogue 5'-guanylylimidodiphosphate (Gpp[NH]p) to inhibit FK-stimulated AC activity was also decreased in pancreatic acinar membranes from ethanol-treated rats. Gpp[NH]p was a much less potent inhibitor of SS binding in the pancreatic acinar membranes from chronic ethanol-treated animals than in those from controls, suggesting a change of Gi. A significant reduction in the number of 125I-Tyr11-SS receptors was observed after ethanol ingestion, when compared with control values. Two weeks after the replacement of the ethanol solution by water, the ethanol effect on the parameters cited above persisted. At week 7 of withdrawal, these parameters reached the level of water controls. Ethanol administration did not affect either the number or the affinity of secretin receptors as compared to control values which suggests that the change in SS binding is not a non-specific effect. Neither chronic ethanol consumption nor withdrawal affected somatostatin-like immunoreactivity (SSLI). These results suggest that the attenuated inhibition of AC by SS in pancreatic acinar membranes from ethanol-treated rats and ethanol withdrawal (2 weeks) rats may be caused by decreases in both Gi activity and in the number of SS receptors. Alternatively, an uncoupling of SS receptors from Gi and/or a decrease in the level of functional Gi may result in both a decrease in apparent Bmax for SS binding and in SS-mediated inhibition of AC. Since SS has been suggested to be an inhibitor of basal and cholecystokinin (CCK)- and/or secretin-stimulated exocrine pancreatic secretion, it is tempting to speculate that the impairment of the SS receptor/effector system seen in the present study can participate in the increase of basal pancreatic exocrine secretion described after chronic ethanol consumption.
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PMID:Ethanol-induced modification of somatostatin-responsive adenylyl cyclase in rat exocrine pancreas. 762 57

Somatostatin 14 and various derivatives protect rat gastric mucosa against ethanol-induced lesions. Their mechanism of action is unknown. We investigated the effect of two somatostatin derivatives, octreotide and 5-(L)-citrullin-octreotide, on ethanol-induced hemorrhagic lesions, microcirculatory stasis and elevated vascular permeability in the rat stomach, with the goal to elucitate the pharmacological and microcirculatory mechanisms behind the gastroprotective effect. Radioligand studies revealed a high affinity of octreotide for the somatostatin receptor (IC50 = 5 x 10(-10) mol/l), in contrast to 5-(L)-citrullin-octreotide (IC50 = 3 x 10(-6) mol/l). This was in good agreement with the inhibition of growth hormone release from rat anterior pituitary cells (octreotide: IC50 = 1.2 x 10(-10) mol/l; 5-(L)-citrullin-octreotide: IC50 = 3 x 10(-6) mol/l). Intragastric administration of ethanol to rats resulted in lesions of the gastric mucosa affecting 18.9 +/- 3.1% of the area of the glandular stomach. Octreotide reduced the area to 6.4 +/- 1.7% (P < 0.05). The dose-response curve was bell-shaped. 5-(L)-citrullin-octreotide was totally devoid of any protective activity (dose range: 0.1 ng/kg to 0.1 mg/kg). We further investigated the effect of the two peptides on ethanol-induced microcirculatory stasis and elevated vascular permeability. Ethanol in a concentration of 50% induced an increase in microvascular permeability, measured by the extravasation of the tracer fluorescein-isothiocyanate-dextran (molecular weight 150,000). Pretreatment with octreotide (0.1 ng/kg s.c.) prevented stasis and reduced capillary permeability significantly. 5-(L)-citrullin-octreotide had no effect on ethanol-induced microcirculatory stasis and elevated vascular permeability in rat gastric mucosa.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The somatostatin analogue octreotide protects against ethanol-induced microcirculatory stasis and elevated vascular permeability in rat gastric mucosa. 798 53

To examine the possible involvement of somatostatin in growth hormone modifications induced by ethanol, we examined: (1) the effects of chronic ethanol exposure of cultured hypothalamic neurons on somatostatin content and mRNA levels; (2) the acute effect of ethanol on somatostatin release stimulated by N-methyl-D-aspartate (NMDA). The results showed that 8 days of ethanol exposure (10-100 mM) did not decrease somatostatin content or somatostatin mRNA levels. Ethanol treatment alone had no significant effect on cell morphology or on protein content. In contrast, acute application of ethanol in 8 day-old cultures significantly reduced (50 mM) or completely blocked (100 mM) somatostatin release elicited by 50 microM NMDA without modifying basal release. We conclude that chronic ethanol treatment to concentrations up to 100 mM has no effect on somatostatin biosynthesis in fetal rat hypothalamic neurons, while weaker concentrations decrease NMDA-induced somatostatin release.
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PMID:Effect of acute, but not chronic ethanol treatment on somatostatin secretion in rat hypothalamic neurons. 960 84

The incidence of hepatocellular carcinoma (HCC) is increasing in the United States. Several modalities are available for the treatment of HCC, and decisions regarding the optimal choice of therapy are based on tumor burden and severity of liver disease. Classification systems are helpful for prognostic purposes and to guide in the choice of therapy. Surgical resection is a mainstay of therapy for patients with solitary small tumors and preserved liver function (noncirrhotic or Child-Pugh class A cirrhotic patients without portal hypertension). Unfortunately, a minority of patients is eligible for resection, and postoperative recurrence or de novo HCC is common. Liver transplantation offers the best chance of curing HCC in cirrhotic patients. Patients with a solitary tumor less than 5 cm or no more than three tumors each 3 cm or less have a survival rate of 70% with less than 20% recurrence at 5 years. Access to liver transplantation is limited by organ availability, and tumor progression during the waiting period can lead to ineligibility. Ethanol injection and radiofrequency ablation are effective modalities to ablate small tumors (generally <5 cm) in patients who are not candidates for resection or liver transplantation. These modalities can also be used to treat HCC prior to liver transplantation. Transarterial chemoembolization is used to treat patients with multifocal or large HCC who are ineligible for other therapies. Chemotherapeutic agents are infused into the tumor via the hepatic artery along with embolic material in order to induce tumor necrosis. This technique should be used in selective patients with relatively preserved liver function, absence of portal vein thrombosis, or encephalopathy. Limited data exist to support the use of this modality as a primary treatment option for small HCC. Chemotherapeutic or hormonal therapies have a limited role in the management of patients with HCC. Despite mixed outcomes, we routinely use the somatostatin analog octreotide in advanced, multifocal HCC. Emerging therapies should focus on treatment of small tumors and targeted pharmacologic therapy for advanced disease.
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PMID:Treatment of Hepatocellular Carcinoma. 1458 35

The proopiomelanocortin-derived tridecapeptide alpha-melanocyte-stimulating hormone (alpha-MSH) is a neuropeptide that exerts broad anti-inflammatory actions in mammals. This study aimed to investigate the effect of alpha-MSH on ethanol-induced gastric ulcer in rats and to evaluate the involvement of endogenous somatostatin in the actions of the peptide. The rats received 1 mL 75% ethanol or saline orally. alpha-MSH was given (25 micro g/rat; i.p.) alone or following the somatostatin antagonist cyclo-(7-aminoheptanoyl-PH-E-d-Trp-Lys-THR) (10 microM/kg; i.p.) administration. Gastric lesions were scored macroscopically and microscopically following decapitation at 30 min after ethanol challenge. Gastric malondialdehyde (MDA) level, myeloperoxidase (MPO) activity and mast cell counts were assessed. Ethanol-induced gastric hemorrhagic lesions were characterized by increased gastric MDA level, MPO activity and mast cell counts. alpha-MSH treatment decreased the extent of tissue injury and reversed tissue MDA level, MPO activity and mast cell counts. The effect of the peptide on the severity of gastric lesions, MDA level and MPO activity was reversed by the somatostatin antagonist. In conclusion, alpha-MSH is beneficial in a rat model of gastric ulcer via mechanisms which partly involve the endogenous somatostatin.
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PMID:Gastric protection by alpha-melanocyte-stimulating hormone against ethanol in rats: involvement of somatostatin. 1718 7


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